Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Orodispersible minitablets of enalapril for use in children with heart failure (LENA): Rationale and protocol for a multicentre pharmacokinetic bridging study and follow-up safety study

Introduction: Treatment of paediatric heart failure is based on paradigms extensively tested in the adult population assuming similar underlying pathophysiological mechanisms. Angiotensin converting enzyme inhibitors (ACEI) like enalapril are one of the cornerstones of treatment and commonly used off-label in children. Dose recommendations have been extrapolated from adult experience, but the relationship between dose and pharmacokinetics (PK) in (young) children is insufficiently studied. Furthermore, appropriate paediatric formulations are lacking. Within the European collaborative project LENA, a novel formulation of enalapril orodispersible minitablets (ODMT), suitable for paediatric administration, will be tested in (young) children with heart failure due to either dilated cardiomyopathy or congenital heart disease in two pharmacokinetic bridging studies. Paediatric PK data of enalapril and its active metabolite enalaprilat will be obtained. In a follow-up study, the safety of enalapril ODMTs will be demonstrated in patients on long-term treatment of up to 10 months. Furthermore, additional information about pharmacodynamics (PD) and ODMT acceptability will be collected in all three studies. Methods and Analysis: Phase II/III, open-label, multicentre study. Children with dilated cardiomyopathy (DCM) (n=25; 1 month to less than 12 years) or congenital heart disease (CHD) (n=60; 0 to less than 6 years) requiring or already on ACEI will be included. Exclusion criteria include severe heart failure precluding ACEI use, hypotension, renal impairment, hypersensitivity to ACEI. For those naive to ACEI up-titration to an optimal dose will be performed, those already on ACEI will be switched to an expected equivalent dose of enalapril ODMT and optimised. In the first 8 weeks of treatment, a PK profile will be obtained at the first dose (ACEI naive patients) or when an optimal dose is reached. Furthermore, population PK will be done with concentrations detected over the whole treatment period. PD and safety data will be obtained at least at 2-weeks intervals. Subsequently, an intended number of 85 patients will be followed-up up to 10 months to demonstrate long-term safety, based on the occurrence of (severe) adverse events and monitoring of vital signs and renal function. Ethics and dissemination: Clinical Trial Authorisation and a favourable ethics committee opinion were obtained in all five participating countries. Results of the studies will be submitted for publication in a peer-reviewed journal. Trial registration numbers: EudraCT 2015-002335-17, EudraCT 2015-002396-18, EudraCT 2015-002397-21

Intracranial pressure monitoring in patients with acute brain injury in the intensive care unit (SYNAPSE-ICU): an international, prospective observational cohort study

Background: The indications for intracranial pressure (ICP) monitoring in patients with acute brain injury and the effects of ICP on patients’ outcomes are uncertain. The aims of this study were to describe current ICP monitoring practises for patients with acute brain injury at centres around the world and to assess variations in indications for ICP monitoring and interventions, and their association with long-term patient outcomes. Methods: We did a prospective, observational cohort study at 146 intensive care units (ICUs) in 42 countries. We assessed for eligibility all patients aged 18 years or older who were admitted to the ICU with either acute brain injury due to primary haemorrhagic stroke (including intracranial haemorrhage or subarachnoid haemorrhage) or traumatic brain injury. We included patients with altered levels of consciousness at ICU admission or within the first 48 h after the brain injury, as defined by the Glasgow Coma Scale (GCS) eye response score of 1 (no eye opening) and a GCS motor response score of at least 5 (not obeying commands). Patients not admitted to the ICU or with other forms of acute brain injury were excluded from the study. Between-centre differences in use of ICP monitoring were quantified by using the median odds ratio (MOR). We used the therapy intensity level (TIL) to quantify practice variations in ICP interventions. Primary endpoints were 6 month mortality and 6 month Glasgow Outcome Scale Extended (GOSE) score. A propensity score method with inverse probability of treatment weighting was used to estimate the association between use of ICP monitoring and these 6 month outcomes, independently of measured baseline covariates. This study is registered with ClinicalTrial.gov, NCT03257904. Findings: Between March 15, 2018, and April 30, 2019, 4776 patients were assessed for eligibility and 2395 patients were included in the study, including 1287 (54%) with traumatic brain injury, 587 (25%) with intracranial haemorrhage, and 521 (22%) with subarachnoid haemorrhage. The median age of patients was 55 years (IQR 39–69) and 1567 (65%) patients were male. Considerable variability was recorded in the use of ICP monitoring across centres (MOR 4·5, 95% CI 3·8–4·9 between two randomly selected centres for patients with similar covariates). 6 month mortality was lower in patients who had ICP monitoring (441/1318 [34%]) than in those who were not monitored (517/1049 [49%]; p<0·0001). ICP monitoring was associated with significantly lower 6 month mortality in patients with at least one unreactive pupil (hazard ratio [HR] 0·35, 95% CI 0·26–0·47; p<0·0001), and better neurological outcome at 6 months (odds ratio 0·38, 95% CI 0·26–0·56; p=0·0025). Median TIL was higher in patients with ICP monitoring (9 [IQR 7–12]) than in those who were not monitored (5 [3–8]; p<0·0001) and an increment of one point in TIL was associated with a reduction in mortality (HR 0·94, 95% CI 0·91–0·98; p=0·0011). Interpretation: The use of ICP monitoring and ICP management varies greatly across centres and countries. The use of ICP monitoring might be associated with a more intensive therapeutic approach and with lower 6-month mortality in more severe cases. Intracranial hypertension treatment guided by monitoring might be considered in severe cases due to the potential associated improvement in long-term clinical results. Funding: University of Milano-Bicocca and the European Society of Intensive Care Medicine

Intracranial pressure monitoring in patients with acute brain injury in the intensive care unit (SYNAPSE-ICU): an international, prospective observational cohort study

Background: The indications for intracranial pressure (ICP) monitoring in patients with acute brain injury and the effects of ICP on patients’ outcomes are uncertain. The aims of this study were to describe current ICP monitoring practises for patients with acute brain injury at centres around the world and to assess variations in indications for ICP monitoring and interventions, and their association with long-term patient outcomes. Methods: We did a prospective, observational cohort study at 146 intensive care units (ICUs) in 42 countries. We assessed for eligibility all patients aged 18 years or older who were admitted to the ICU with either acute brain injury due to primary haemorrhagic stroke (including intracranial haemorrhage or subarachnoid haemorrhage) or traumatic brain injury. We included patients with altered levels of consciousness at ICU admission or within the first 48 h after the brain injury, as defined by the Glasgow Coma Scale (GCS) eye response score of 1 (no eye opening) and a GCS motor response score of at least 5 (not obeying commands). Patients not admitted to the ICU or with other forms of acute brain injury were excluded from the study. Between-centre differences in use of ICP monitoring were quantified by using the median odds ratio (MOR). We used the therapy intensity level (TIL) to quantify practice variations in ICP interventions. Primary endpoints were 6 month mortality and 6 month Glasgow Outcome Scale Extended (GOSE) score. A propensity score method with inverse probability of treatment weighting was used to estimate the association between use of ICP monitoring and these 6 month outcomes, independently of measured baseline covariates. This study is registered with ClinicalTrial.gov, NCT03257904. Findings: Between March 15, 2018, and April 30, 2019, 4776 patients were assessed for eligibility and 2395 patients were included in the study, including 1287 (54%) with traumatic brain injury, 587 (25%) with intracranial haemorrhage, and 521 (22%) with subarachnoid haemorrhage. The median age of patients was 55 years (IQR 39–69) and 1567 (65%) patients were male. Considerable variability was recorded in the use of ICP monitoring across centres (MOR 4·5, 95% CI 3·8–4·9 between two randomly selected centres for patients with similar covariates). 6 month mortality was lower in patients who had ICP monitoring (441/1318 [34%]) than in those who were not monitored (517/1049 [49%]; p<0·0001). ICP monitoring was associated with significantly lower 6 month mortality in patients with at least one unreactive pupil (hazard ratio [HR] 0·35, 95% CI 0·26–0·47; p<0·0001), and better neurological outcome at 6 months (odds ratio 0·38, 95% CI 0·26–0·56; p=0·0025). Median TIL was higher in patients with ICP monitoring (9 [IQR 7–12]) than in those who were not monitored (5 [3–8]; p<0·0001) and an increment of one point in TIL was associated with a reduction in mortality (HR 0·94, 95% CI 0·91–0·98; p=0·0011). Interpretation: The use of ICP monitoring and ICP management varies greatly across centres and countries. The use of ICP monitoring might be associated with a more intensive therapeutic approach and with lower 6-month mortality in more severe cases. Intracranial hypertension treatment guided by monitoring might be considered in severe cases due to the potential associated improvement in long-term clinical results. Funding: University of Milano-Bicocca and the European Society of Intensive Care Medicine